To our knowledge there are no effective pharmacologic treatments for marijuana dependence. One subgroup that might benefit from a targeted pharmacologic intervention is marijuana-dependent individuals who have depressive disorders. The prevalence of current depression in marijuana-dependent individuals in clinical samples ranges from 20-24%. This rate is substantially higher than what is found in the general population (2-10%). Given the comorbidity of depression and marijuana dependence, pharmacotherapies aimed at treating these dually-disordered patients may be particularly effective. Venlafaxine-extended release, a once-a-day medication that is commonly used to treat depression, is a promising option. Recent work completed by our group has found that a reduction in psychiatric symptoms is correlated with a reduction in substance use. However, abstinence has been more elusive. It is becoming increasingly clear that no one intervention, whether it be pharmacologic or nonpharmacologic, will be successful in treating substance-dependent individuals with comorbid depression. Instead, an integrated treatment is needed. We therefore propose a placebo-controlled trial of the venlafaxine extended release, Ven-XR, an antidepressant, which is both a selective serotonin reuptake inhibitor and a noradrenergic reuptake inhibitor, in a sample of marijuana-dependent patients with current major depression. All patients in the trial will receive weekly motivational enhancement and cognitive behavior therapy. The following specific aims will be addressed: 1. To determine whether Ven-XR, along with motivational enhancement/relapse prevention therapy, reduces symptoms of depression compared to placebo. 2. To determine whether Ven-XR, along with motivational enhancement/relapse prevention therapy, increases the achievement of sustained abstinence. 3. To examine the relationship between medication treatment, mood improvement, cognitive functioning and improvement in marijuana abuse using mediational analyses.